November 15, 2018

Of Mice and Humans

In recent years an increasing emphasis has been placed on scientific studies that derive data from humans rather than from animals. This is in part because many people are uncomfortable with the image of cute little furry creatures being subjected to tortuous experiments (think Watership Down) and also because animal experiments may not predict human responses under similar conditions. Having a contrarian streak buried deep within my genome, I find myself paddling against this tide and often find myself unwilling to ignore animal trials, particularly when they seem to provide useful information. In fact, it feels as if I keep a running list in the back of my mind of interesting animal trials that may be useful.

Case in point is the November 2018 paper by Carmit Levy from Tel Aviv University. Levy and colleagues have been examining the mechanisms that protect the skin from sun damage. Turns out there are two different mechanisms that protect the skin. The first response is inflammation, which in turn triggers an immune response that repairs radiation damaged DNA and increases cell multiplication in delicate skin layers. The second protective mechanism is the one that produces the dark pigment melanin and leads to tanned skin, acting as a natural sunscreen. The inflammatory stress response is rapid, taking only minutes from UV exposure onset, while melanin production is slower, taking days to respond.

In fact, the melanin response takes about two days, and this leads to a peculiar phenomenon. Levy reports that “…UVB exposure every other day induces significantly more skin pigmentation than the higher frequency of daily exposure, without an associated increase in stress responses.”1

Think about it. If you vacation at the beach for a week, and spend every other day indoors, you’ll end up tanner than if you spent every day out in the sun. At the same time there will be less UV radiation damage, less sunburn, less genetic damage, and theoretically lower cancer risk. This is counterintuitive for sure. Everyone assumes the opposite would be true. The researchers first proved this response occurs in mice and then used human skin cells to confirm the same reaction occurs in people. It’s useful for us to know things work this way and I for one am glad not to volunteer for experiments like this.

Now that we know this we can caution our patients to work up their tans with alternate day sun exposure. “You won’t believe this, but you will tan faster and safer.”

Anther recent mouse study caught my attention. Researchers from Quebec City reported in November 2018 that extracts of ashwagandha (Withania somnifera) are protective in a mouse model of amyotrophic lateral sclerosis (ALS). This certainly does not mean that it will work in humans but pretty much nothing has been proven to work in humans, and since there is little to fear from taking ashwagandha, the obvious question is why not? 2 Based on this scant evidence from mice, we can say, “Might help, won’t hurt.” And that strikes me as a superior position to saying, “There’s nothing we can do to help.”

While thinking about ashwagandha there is another study perhaps even worse than these other two. Back in 2017, a study suggested that this herbal extract was useful in ‘priming’ cancer cells for chemotherapy, that it increased the reactive oxygen species (ROS) in cancer cells but not in healthy cells, and left them more vulnerable to chemotherapy drugs, in particular cisplatin.3 What was worse about this study? It was not even a mouse experiment. The researchers used human colon cancer cells grown in petri dishes to run this experiment. What if this is mediocre evidence of benefit; if you had colon cancer and were scheduled to receive cisplatin, wouldn’t you want to take some ashwagandha?

Some studies are better than others. Not all human studies are reliable evidence. Something works in one study but not in a second study. No data are really reliable. Everything we know in science is subject to change. We’ve got to remember some practitioners still use pendulums to decide what works. Mice are not the worse choice when looking for benefits.

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